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Abstract
Konzo is a neglected paralytic neurological disease associated with food (cassava) poisoning that affects the world’s poorest children and women of childbearing ages across regions of sub-Saharan Africa. Despite understanding the dietary factors that lead to konzo, the molecular markers and mechanisms that trigger this disease remain unknown. To identify potential protein biomarkers associated with a disease status, plasma was collected from two independent Congolese cohorts, a discovery cohort (n = 60) and validation cohort (n = 204), sampled 10 years apart and subjected to multiple high-throughput assays. We identified that Glutathione Peroxidase 3 (GPx3), a critical plasma-based antioxidant enzyme, was the sole protein examined that was both significantly and differentially abundant between affected and non-affected participants in both cohorts, with large reductions observed in those affected with konzo. Our findings raise the notion that reductions in key antioxidant mechanisms may be the biological risk factor for the development of konzo, particularly those mediated through pathways involving the glutathione peroxidase family.
The search for biomarkers associated with konzo disease has been a long-standing question within the research community. Here, the authors have uncovered a potential biomarker for konzo that is associated with the ability to manage oxidative damage.
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1 Children’s National Hospital, Center for Genetic Medicine Research, Children’s Research Institute, Washington, USA (GRID:grid.239560.b) (ISNI:0000 0004 0482 1586); The George Washington University of Medicine and Health Sciences, Department of Genomics and Precision Medicine, Washington, USA (GRID:grid.253615.6) (ISNI:0000 0004 1936 9510)
2 CHU de Québec - Université Laval Research Center, Computational Biology Laboratory and The Proteomics Platform, Québec City, Canada (GRID:grid.411081.d) (ISNI:0000 0000 9471 1794)
3 UCLA, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718)
4 Children’s National Hospital, Center for Genetic Medicine Research, Children’s Research Institute, Washington, USA (GRID:grid.239560.b) (ISNI:0000 0004 0482 1586)
5 Kinshasa University, Department of Neurology, Kinshasa, Democratic Republic of the Congo (GRID:grid.9783.5) (ISNI:0000 0000 9927 0991)
6 Institut National de Recherche Biomédicale (INRB), Kinshasa, Democratic Republic of the Congo (GRID:grid.452637.1) (ISNI:0000 0004 0580 7727)
7 Kinshasa University, Department of Neurology, Kinshasa, Democratic Republic of the Congo (GRID:grid.9783.5) (ISNI:0000 0000 9927 0991); Institut National de Recherche Biomédicale (INRB), Kinshasa, Democratic Republic of the Congo (GRID:grid.452637.1) (ISNI:0000 0004 0580 7727)
8 University of the Philippines, Manila, Ermita, Biological Models Laboratory, Department of Biochemistry and Molecular Biology, College of Medicine, Manila, Philippines (GRID:grid.11159.3d) (ISNI:0000 0000 9650 2179)
9 University of Nevada, Reno School of Medicine, Department of Microbiology and Immunology, Reno, USA (GRID:grid.266818.3) (ISNI:0000 0004 1936 914X)
10 Michigan State University, Departments of Psychiatry and Neurology & Ophthalmology, East Lansing, USA (GRID:grid.17088.36) (ISNI:0000 0001 2195 6501)
11 University of California, Institute for Clinical and Translational Science, Irvine, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243)
12 Institut National de Recherche Biomédicale (INRB), Kinshasa, Democratic Republic of the Congo (GRID:grid.452637.1) (ISNI:0000 0004 0580 7727); Oregon Health & Science University, Department of Neurology, Portland, USA (GRID:grid.5288.7) (ISNI:0000 0000 9758 5690)